Over the past 11 years, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) team has expanded and refined its computer simulation of HIV disease in order to better address critical questions in HIV management. During the first two years ofthe R37 cycle, the CEPAC project has experienced tremendous growth, outstanding productivity, and increased outreach and collaboration with other NIAID-funded as well as other national and international research groups. During this time, the CEPAC team has published 19 peer-reviewed papers, with one more in press and two others submitted. The specific aims for the next cycle of the grant (2010-2015) address critical areas of HIV clinical care and policy in the United States, while continuing the cutting-edge methodology and applications that have maintained the CEPAC team as an internationally-recognized HIV research effort. The three specific aims for the next phase of the grant are: 1. To examine the issue of when to start antiretroviral therapy in the US, taking into account a newer understanding of HIV disease complications and new approaches to HIV testing. 2. To determine the clinical impact, value and optimal use of both new diagnostic technologies and existing laboratory monitoring tests. 3. To evaluate comprehensive approaches to HIV care that will optimize treatment outcomes in the context of improved survival, an aging population, and an increasing prevalence of co-morbidities. During the next cycle of this project, we will use innovative simulation methods and incorporate new data from the best national sources to deliver high-impact studies that will directly influence HIV treatment guidelines and policies in the United States.